Sci. Aging Knowl. Environ., 29 January 2003
Protein kick-starts skin's repair process
Key Words: PC-derived growth factor acrogranin epithelin/granulin precursor cytokine macrophage neutrophil
Contrary to the clich� that time heals all wounds, injuries in older people mend less efficiently than in young folks. Understanding more about how skin repairs itself could lead to wound treatments for the elderly and others with impaired restorative ability. New work identifies a protein that might initiate the skin's response to wounding and, in combination with other agents, could find therapeutic use.
Sustaining a skin wound instigates an orderly repair response. First a clot forms, which covers and seals the injury. Next, white blood cells descend on the breach, sterilizing the area and sending out a chemical call for help. Structural cells called fibroblasts then lay down a temporary matrix in the damaged region, and endothelial cells form blood vessels as permanent tissue grows back. The entire operation is choreographed by growth factors, which summon specialized cells to the scene and direct cell division as new skin grows. Although some of the key molecules are known, they have not yet found widespread therapeutic application.
While studying the growth factor progranulin, which spurs tumor formation but had not previously been linked to wound healing, molecular biologist Andrew Bateman of McGill University in Montreal and his colleagues found that the protein also resides in inflammatory cells. Its presence there suggested that those cells stimulate wound repair by emitting progranulin, which might induce healing, as other growth factors do. To test this idea, the researchers measured the amount of progranulin messenger RNA at the site of a puncture wound in mice. They found increased quantities in the immune cells that were dispatched to the injury, but it also turned up in endothelial cells and fibroblasts, two types of cells that don't produce progranulin in intact skin.
Having established that reparative cells in the vicinity of freshly damaged skin start manufacturing progranulin, the researchers wondered what would happen if they doused an injury with the protein. Adding progranulin increased the number of white blood cells at the trauma site and caused them to hang around longer than usual. Wounds treated with progranulin also developed nearly twice the number of blood vessels as did those that were left untreated. Progranulin didn't, however, increase the amount of matrix-forming proteins laid down, nor did it speed healing: The wound's size remained the same, regardless of progranulin treatment. "Progranulin kick-starts the healing process," says Bateman, "but in itself is not sufficient to heal the wound." Like a car's ignition key, it gets things going, but something else has to hit the accelerator.
Progranulin, perhaps in concert with other wound-repair molecules, could emerge as a therapeutic tool for those whose healing powers have faltered, Bateman says. The study points scientists in a new direction, says gastric injury repair researcher Andrzej Tarnawski of the University of California, Irvine, who calls the data "innovative and important." Furthermore, the observation that endothelial cells and fibroblasts produce progranulin suggests that these cells might play a more extensive role in repair than previously thought, says Bateman. Although more work remains to be done before progranulin's clinical value becomes clear, that's one deficit that time will surely heal.
--Caroline Seydel; suggested by Amir Sadighi Akha
Z. He, C. H. P. Ong, J. Halper, A. Bateman, Progranulin is a mediator of the wound response. Nat. Med., 13 January 2003 [e-pub ahead of print]. [Abstract/Full Text]
January 29, 2003 Citation: C. Seydel, Healing Power. Science's SAGE KE (29 January 2003), http://sageke.sciencemag.org/cgi/content/full/sageke;2003/4/nw16
Science of Aging Knowledge Environment. ISSN 1539-6150